PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway
PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway
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DOI：
10.1186/s13046-019-1260-6
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发表时间：
2019-06-13
影响因子：
11.3
通讯作者：
Li, Lianhong
中科院分区：
文献类型：
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作者：
Gao, Xue;Qin, Tao;Li, Lianhong
研究背景长链非编码RNA PTENP 1是抑癌基因PTEN的假基因，在包括乳腺癌在内的多种恶性肿瘤中通过调控PTEN表达发挥抑癌作用。然而，PTENP 1/miR-20 a/PTEN轴是否存在及其在BC进展中的作用机制尚不清楚。采用CCK 8法、集落形成法、EDU法和Ki 67染色法检测细胞增殖情况。transwell法检测细胞迁移和侵袭能力。流式细胞术、JC-1和TUNEL检测细胞凋亡的发生。结果分析了临床乳腺癌标本和细胞系中PTENP 1和PTEN的表达，发现PTENP 1和PTEN与乳腺癌细胞系恶性程度和临床预后密切相关。此外，PTENP 1的改变影响BC细胞的增殖、侵袭、肿瘤发生和对阿霉素（ADR）的化学抗性。生物信息学分析和双荧光素酶报告基因分析预测PTENP 1是miR-20 a的直接靶点，阐明了miR-20 a对BC侵袭性表型的替代作用。此外，PTENP 1作为miR-20 a的内源性海绵调控PTEN的表达，通过激活磷脂酰肌醇-3激酶（PI 3 K）/AKT通路介导BC细胞增殖、侵袭和耐药。结论PTENP 1/miR-20 a/PTEN轴参与了BC细胞的恶性行为，提示PTEN可能通过PI 3 K/Akt途径介导BC细胞的恶性行为。靶向PTENP 1/miR-20 a/PTEN可能为BC提供潜在的诊断和治疗策略。
BackgroundLong non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, has been reported to exert its tumor suppressive function via modulation of PTEN expression in many malignancies, including breast cancer (BC). However, whether the PTENP1/miR-20a/PTEN axis exists and how it functions in BC progression remains elusive.MethodsThe levels of PTENP1, PTEN and miR-20a were measured by qRT-PCR. Furthermore, the breast cancer cells proliferation was further measured by CCK8 assay, colony formation assays, EDU and Ki67 staining. The migratory and invasive ability was determined by transwell assay. Flow cytometry, JC-1 and TUNEL assays were conducted to show the occurrence of apoptosis. Xenograft model was used to show the tumorigenesis of breast cancer cells.ResultsWe analyzed PTENP1 and PTEN levels in clinical BC samples and cell lines, and found that PTENP1 and PTEN were confirmed and closely correlated with the malignancy of BC cell lines and poor clinical prognosis. Moreover, alteration of PTENP1 affects BC cell proliferation, invasion, tumorigenesis and chemoresistance to adriamycin (ADR). Bioinformatic analysis and dual-luciferase reporter gene assay predicted that PTENP1 was a direct target of miR-20a, which was clarified an alternative effect on BC aggressiveness phenotype. In addition, PTENP1 functioned as an endogenous sponge of miR-20a to regulate PTEN expression, which mediated BC cells proliferation, invasion and drug resistance via activation the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. PI3K inhibitor LY294002 or siAkt also prevented BC cells progression.ConclusionCollectively, these data indicated that PTENP1/miR-20a/PTEN axis involved in the malignant behaviors of BC cells, illuminating the possible mechanism mediated by PTEN via PI3K/Akt pathway. Targeting PTENP1/miR-20a/PTEN may provide a potential diagnosis and treatment strategy for BC.